Metabolism Of Kidney Flashcards
Blood supply differences in kidney
. 90-95% of renal blood passes through cortex and uses 8% of oxygen in blood
. 5-10% of renal blood passes through medulla and uses 80% of oxygen in that blood
. Medulla more vulnerable to anoxic shock
Roles of kidney
. Makes urine to excrete waste, regulate serum pH, electrolytes, and water
. Has enzymes for gluconeogenesis
. Acts as endocrine gland: synthesizes and releases EPO, renin
. Contains enzymes for vit. D metabolism important for serum Ca, ,phosphate, and bone metabolism regulation
Components of urine synthesis
. Filtration
. Reabsorption
. Secretion
Sequence of events in filtration
. Blood enters afferent arterioles
. GFR depends on bp
. Filters through 3 layers
. Capillary endothelium: 100x more permeable than other capillaries
. Basement membrane: composed of highly negatively charged glycoproteins and proteoglycans
. Single layer of epithelial cells (podocytes) w/ foot processes that interdigitate w/ one another
What gets filtered in kidney?
. 20% plasma volume through kidney forced through filter to become ultrafiltrate
. Collects in Bowman’s capsule
Ultrafiltrate contents
. Plasma H2O
. Small solutes (glucose, NaCl, urea, AA)
Ultrafiltrate does NOT contain _____
. Cells or cell-like structure
. Proteins beyond a certain limit ( larger and neg. charges proteins do NOT go through)
Glomerular filtration rate
. Measured by injecting radioactive substance that’s filtered in kidney and not reabsorbed by tubules
. Takes blood samples over several hours
. dec. GFR is sign of diminished kidney function
Reabsorption in kidney
. Movement of material from tubule lumen into capillary
. Much if what is filtered is reabsorbed
. Requires energy
Secretion in kidney
. Movement of material from capillaries into tubule lumen
. Requires energy
Modes of transport in kidney tubules
. Primary active transport (NA-K-ATPase)
. Secondary active transport (glucose/Na cotransport and amino acid-Na cotransport)
. Pinocytosis and endocytosis
Important indicators of renal function
Levels of urea and creatinine
Azotemia
. Asymptomatic
. Nitrogenous waste products that accumulate in patient’s serum
Uremia
. Symptomatic (nausea and vomiting) nitrogenous waste product build up in patient’s serum
Renal threshold
. Substance that are absorbed have limit to rate at which solute can be transported
. When limit is surpassed the excess is secreted
. Glucose threshold is 220 mg/dl
Endogenous compounds secreted by tubules in kidney
. Urate, creatinine, bile acid salts
Exogenous compounds secreted in kidney tubules
. Penicillin
. Salicylate
What determines final composition of urine?
. Excretion = filtration-absorption+secretion
PH of urine is between _____
4.4 and 8
Reabsorption of bicarbonate
. Most passes through filter and is reabsorbed by transporters in tubule cells
Kidney excretion of phosphate and other acids
. Molecules that have pK in range of pH of urine can pick up proton and carry out in urine
. Occurs w/ any acid that can bind H and carry it out in urine
What happens in kidneys during diabetic ketoacidosis
. Inc. of ketones
. Compounds filtered and appear in tubule fluid
. As urine pH dec., these compounds begin to serve as buffers that can carry H out of body in urine
Excretion of ammonia/ammonium
. NH4 is major urinary acid (1/2-2/3 daily acid load excreted w/ this)
. Preserves Na and K reserves in prolonged acidosis (other acids need this)
Aerobic vs. anaerobic metabolism in kidney
. Uses 10% of O2 the body uses
. Renal cortex more highly oxidative then medulla
. Medulla depends on glycolysis and is sensitive to low [O2]
Glucose utilized in renal medulla is produced in ___
Renal cortex
Major renal fuel used in normal (fed) person
Lactate (45%)
Major renal fuel in acidosis
Glutamine
Major renal fuel in a fasted state
. Fatty acids
Gluconeogenesis in kidney
. Can make 20-50% as much glucose as liver
. Predominantly associated w/ cortex
. Cortex is highly oxidative tissue w/ high ATP synthetic ability
. Substrates: Gln, lactate, citrate, alpha-ketoglutarate
. Important in starvation and acidosis
If acidosis is treated w/ alkali administration, then renal gluconeogenesis is___
Not stimulated
Non-excretory mechanism for kidney pH regulation
. Conversion of certain organic acids to glucose
Glutamine in kidney
. Gln taken up from blood
. Renal uptake regulated by pH (inc. uptake w/ acidosis) and glucocorticoids (stimulate glutaminase and Gln metabolism)
Glutamine metabolism in kidney
. Glutaminase converts Gln to Glu and releases 2 NH3 molecules for H excretion
. Glutamate dehydrogenase converts Glu to alpha-ketoglutarate that can be used in ATP or as substrate for gluconeogenesis
Erythropoietin
. Polypeptide hormone
. Synthesized in response to reduction in renal PO2
. Stimulates bone marrow to inc. production of erythrocytes
People w. Impaired renal function and anemia are given ___
Exogenous EPO
Renin
. Protease
. Made in response to signals from granular cells that ac as intrarenal baroreceptors
. When pressure drops the synthesis of renin is stimulated
Renin-angiotensin system
. Angiotensinogen (plasma protein in liver) gets cleaved to angiotensin I through renin
. angiotensin I is converted to angiotensin II via angiotensin-converting enzyme (ACE)
Rate limiting step in RAAS
Renin
Where does RAAS occur?
. Exists in plasma and vascular surface of blood vessels throughout body, esp. in kidneys
Angiotensin II functions
. Potent vasoconstrictor, inc. bp
. Inc. synthesis of aldosterone, steroid hormone, that inc. Na reabsorption
. Inhibits renin synthesis
ACE inhibitors
. Captopril
. Benazepril
. Enalapril
Angiotensin II receptor blockers
. Irbesartan
. Candesartan
. Losartan
. Valsartan
Vitamin D
. Dietary or synthesized from cholesterol in skin
. Regulates serum Ca and phosphate
. Interacts w/ bone, kidney, and intestine
. Promotes absorption of Ca in intestine
. Liver converts it to circulating form of Vit D
Kidney converts it to active or inactive form
Vitamin D deficiency
. Causes inability to absorb dietary Ca
. Results in bone loss
Chronic renal failure in relation if vit. D
. Results in Inability to produce active vit D
. Bone Ca becomes depleted
. Inc. retention of Pi because kidney can’ excrete it causing high serum phosphate
. When Pi is hig, less Ca can remain in solution
. Leads to bone loss and soft tissue calcification
. Treatment: high Ca diet, vit. D supplements, Pi reduction w/ Pi binding antacids
Symptoms associated w/ kidney failure
. High bp . Back pain just below rib cage . Frequent urination . Rusty or brown colored Urine . Swelling edema of the feet and ankles
Serum levels elevated in patients w/ kidney failure
. Urea
. Creatinine
. Uric acid
Urinalysis of someone w/ chronic kidney disease
. GFR dec. w/ inc. damage
. Urinary protein inc.
. Urinary blood cells inc.
. Urine volume (too little not enough filtration, too much means inability to concentrate urine)
Oliguria
Very little urine production
Kidney not filling endocrine duties will cause ___
. Lack of EPO: low hematocrit, low rbcs, tiredness, malaise
. Lack of kidney function: hypertension
Acute renal failure
. Rapid and usually reversible deterioration of renal function
. Pre-renal causes: blood loss, hemorrhage, CHF
. Renal causes: bacterial infections, intoxins, rhabdmyolysis
. Postrenal: cancer, obstruction of ureter
Rhabdmyolysis
. Damage to skeletal muscle causing myoglobin release
. Appearance of myoglobin in blood and urine
. Myoglobin extremely damaging to kidneys
. Caused by: trauma, excessive exertion in heat, crush syndrome
Chronic renal failure
. Slower, progressive, irreversible loss of renal function
. DM causes 40% cases, hypertension 20%
. 5 stages (1 being slight damage, 5 requiring dialysis or transplant)
